Thrombin-mediated release of factor VIII antigen from human umbilical vein endothelial cells in culture.
We have examined the effects of purified human alpha-thrombin on factor VIII antigen (FVIII-Ag) release by human umbilical vein endothelial cells in culture. Alpha-thrombin induced a time and dose-dependent release of FVIII-Ag into supernatant medium. Alpha-thrombin-mediated FVIII-Ag release was not dependent on protein synthesis and was observed in both serum-free and serum-containing media. FVIII-Ag release, however, was prevented when the serine esterase activity of thrombin was inhibited. Pretreatment of human endothelial cells with alpha-thrombin, but not diisofluorophosphate-thrombin, prevented subsequent FVIII-Ag release by alpha-thrombin. Thrombin-mediated FVII-Ag release was not associated with significant 51Cr release from prelabeled endothelial monolayers. We conclude that alpha-thrombin induces release of preformed FVIII-Ag from human umbilical vein endothelial cells by a receptor-independent, nonlytic mechanism requiring serine esterase activity.
D000941:Antigens / Q000378:metabolism; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004727:Endothelium / Q000276:immunology; D005169:Factor VIII / Q000276:immunology*; D006629:Hirudins / Q000494:pharmacology; D007531:Isoflurophate / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology*; D014107:Tosyllysine Chloromethyl Ketone / Q000494:pharmacology; D014471:Umbilical Veins / Q000187:drug effects / Q000276:immunology*
D000941:Antigens; D006629:Hirudins; D007531:Isoflurophate; D014107:Tosyllysine Chloromethyl Ketone; D005169:Factor VIII; D003513:Cycloheximide; D013917:Thrombin